Opposite control mediated by central 5-HT1A and non-5-HT1A (5-HT1B or 5-HT1C) receptors on periaqueductal gray aversion

Jenck, F.; Broekkamp, C.L.E.; Delft, A. M. L. Van

doi:10.1016/0014-2999(89)90847-9

Cited by 56 publications

(16 citation statements)

References 8 publications

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“…There is also some controversy concerning the role of 5-HT 2 receptors in aversion. In agreement with previously reported results (Schenberg and Graeff 1978), Jenck et al (1989) found that the nonselective 5-HT receptor antagonists metergoline and mianserin decreased the threshold of escape from electrical stimulation of the dPAG. However, the selective 5-HT 2 -receptor antagonist ketanserin had the opposite effect.…”

Section: -Ht and The Pagsupporting

confidence: 89%

“…For instance, systemically injected drugs may be acting mainly on pre-synaptic receptors located outside the PAG. In this regard, Beckett and Marsden (1997) have shown that peripheral injection of 8-OH-DPAT had a pro-aversive effect (like in the results by Jenck et al 1989), whereas intra-PAG injection of the same drug had an anti-aversive effect on chemically induced defense. A likely explanation for this difference suggests that the peripherally injected 8-OH-DPAT stimulates autosomic 5-HT 1A receptors localized in the cell bodies of DRN 5-HT neurons, which inhibit neuronal firing (Aghajanian 1992).…”

Section: -Ht and The Pagmentioning

confidence: 81%

“…However, Jenck et al (1989) arrived at an opposite view, namely that stimulation of 5-HT 1A receptors was pro-aversive. Since these researchers used systemic injection of drugs and a procedure in which rats were trained to jump over a ridge separating the two compartments of a shuttle box the interpretation of these results in terms of PAG mechanisms is not as ease as with intracerebral injection.…”

Section: -Ht and The Pagmentioning

confidence: 93%

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On serotonin and experimental anxiety

Graeff¹

2002

Psychopharmacology

184

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Section: -Ht and The Pagsupporting

confidence: 89%

Section: -Ht and The Pagmentioning

confidence: 81%

Section: -Ht and The Pagmentioning

confidence: 93%

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On serotonin and experimental anxiety

Graeff¹

2002

Psychopharmacology

184

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“…However, this model also revealed paradoxical drug effects. For example, the panic-provoking drug mCPP displayed marked antiaversive action in this test [57]. Similar effects were obtained following acute injection of the SSRIs¯uox-etine [60] and¯uvoxamine [62] which were both found to potentiate panic reactions in PD patients at the initiation of treatment [34,88].…”

Section: Panic Disorder (Pd)mentioning

confidence: 56%

Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic

Blanchard

Griebel

Blanchard

2001

Neuroscience &Amp; Biobehavioral Reviews

410

251

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The natural defensive behaviors of laboratory mice have been evaluated in both seminatural and highly structured situations; and characterized in terms of eliciting stimuli, response to pharmacological agents, behavior patterns, and outcome or effect on the social and physical environment. The defense patterns of laboratory mice and rats are generally similar, but mice show risk assessment on initial exposure to highly threatening stimuli while rats do not, while rats display alarm vocalizations, missing in mice. Quantitative differences in freezing and¯ight for laboratory mice and rats appear to largely re¯ect domestication effects, with wild mice and rats more similar to each other. This nexus of detailed within-species and comparative data on defense patterns makes it possible to reliably elicit speci®c defenses in mice or rats in an experimental context, providing well-validated assays of the natural defensive behaviors themselves, as opposed tò models' of defense.The mouse±rat comparisons indicate considerable cross-species generality for these defense patterns, as does a scattered but considerable literature on other mammalian species, generally involving ®eld studies and typically focusing on those aspects of defensive behavior that are visible at a distance, such as vigilance, or¯ight. Although potential homologies between normal mouse and human defense systems should ideally involve all four pattern components (stimulus, organismic factors, response characteristics, outcome), predictive validity in terms of response to drugs active against speci®c defensive psychopathology is the most extensively investigated of these. Flight, as measured in the Mouse Defense Test Battery shows a consistently appropriate response to panicolytic, panicogenic, and panic-neutral drugs, while some other predictive`panic models' (dPAG-stimulation; DMH-inhibition; possibly conditioned suppression of drinking paradigms) also elicit and (indirectly) measure behaviors potentially related to¯ight. Models unrelated to¯ight (e.g. ultrasonic vocalization to conditioned stimuli); or for which¯ight elements may a relatively minor contributor to the behavior measured (Elevated T-maze) are less predictive of panicolytic or panicogenic action. These ®ndings indicate that natural defensive behaviors provide a well-characterized pattern for analysis of effects of genetic or other physiological manipulations in the mouse, and may also serve as a model for analysis of defenserelated human psychopathology. q 2001 Elsevier Science Ltd. All rights reserved. The recent explosion of genetic techniques and genetically modi®ed animals has greatly exacerbated the need for comprehensive, natural, models or assays of behavior that are relevant to mice, the mammalian species of choice for genetic research [25]; and has additionally focused attention on issues of construction and validation of these tests.Minimally, a behavioral model/assay should enable the reliable elicitation and measurement of a qualitatively consistent behavior pattern for ...

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“…Paradoxical responses to 5HT drugs have been established to occur in some models. For instance, the 5HT agonist 1-(3-chlorophenyl) piperazine (mCPP) is "anxiogenic" in man and in a number of animal models (Charney et al 1987;Kennett et al 1989;Whitton and Curzon 1990) but is actually "anxiolytic" in one-way active avoidance (Moyer and Lucki I985), response to electrical stimulation of the dorsal periaqueductal gray (DPAG) (Jenck et al 1989) and isolation-induced ultrasonic calls in the rat pup (Winslow and Insel 1991). It reduced baseline startle responses (an "anxiolytic" effect), but left "fear-potentiated startle" untouched (Mansbach and Geyer 1988).…”

Section: Paradoxical Effects Of 5ht Drugs In Animal Modelsmentioning

confidence: 98%

5HT drugs in animal models of anxiety

1993

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It has been widely accepted that 5HT neurones promote anxiety, in humans as well as in animal models. This could be termed the "classic" hypothesis and it has led to a determined search for drugs which reduce 5HT function, especially agents which have selective actions at 5HT receptor subtypes. However, these novel agents tend to have weak and/or variable effects in animal models and more detailed examination of their actions suggests that not all findings are accounted for by the classic hypothesis. There appear to be circumstances in which increased 5HT activity can reduce anxious behaviour. There is increasing evidence for multiple anxiety mechanisms, which may be able to explain differential patterns of drug effects within and between models. Animal models of anxiety may also detect non-anxiety factors: effects on cognition or on impulsivity could be reflected in some models. This could be important in the light of recent evidence that 5HT-selective reuptake inhibitors are effective in impulsivity disorders. The classic hypothesis of 5HT function in anxiety may be only one part of an increasingly complex story. Unravelling the rest of this story is likely to lead to new insights in our understanding of anxiety and related disorders.

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Opposite control mediated by central 5-HT1A and non-5-HT1A (5-HT1B or 5-HT1C) receptors on periaqueductal gray aversion

Cited by 56 publications

References 8 publications

On serotonin and experimental anxiety

On serotonin and experimental anxiety

Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic

5HT drugs in animal models of anxiety

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